Metal nanoparticles (NPs) have a long history of use dating back to the 4th or 5th century B.C.E. The optical properties of conductive gold and silver NPs have been associated with the surface plasmon resonance (SPR) of metals, which when confined to small colloids, is referred to as the localized surface plasmon resonance (LSPR). This phenomenon, in which the free electrons oscillate collectively on the metal surface when irradiated with particular energies of light, causes wavelength dependent absorption and scattering of light and is the source of the colors associated with metal nanoparticles. The size, shape, and composition of the colloidal particles determines the energy of the SPRs, and therefore, control over the synthesis of metal NPs provides an ability to tune the optical properties of the nanometals contained therein.
Since Turkevich et al. first described the synthesis of metal nanoparticles by reduction of cationic noble metal ions in solution (Discuss. Faraday Soc. 11 (1951): 55), colloidal suspensions of various NP morphologies have been accomplished, including gold-silver alloys (Y. Sun et al., Analyst 128 (2003): 686-691), core-shell NPs (D. B. Wolfe et al., Langmiur 15 (1999): 2745), gold nanorods (NRs) (N. R. Jana et al., J. Phys. Chem. B 105(19) (2001): 4065-4067), silver nanosheets (J. Xie et al., ACS nano 1(5) (2008): 429-439, and gold nanocages (J. Chen et al., Nano Lett. 5(3) (2005): 473-477). Hybrid approaches such as silver-shell gold NR core NPs have also been employed (M. Lui et al., J. Phys. Chem. B 108 (2004): 5882-5888).
Surface plasmon resonant metal nanoparticles have broad potential in medical diagnostic and therapeutic applications, due to their relative inertness, sub-100 nm size, unique electromagnetic properties, and strong optical tunability. Accordingly, metal NPs have attracted attention in the biomedical field. For example, linking DNA to gold NPs allows biological interactions to form assemblies of colloidal clusters that change the optical properties of the suspension (C. A. Mirkin et al., Nature 382 (1996): 607-609), which can be detected for diagnostic purposes. Because SPRs enhance many optical processes, including Raman scattering, fluorescence, and two-photon excited luminescence, gold NPs have been used in optical diagnostics (K. Asian et al., Current Opinion in Chemical Biology 9 (2005): 538-544) and as contrast agents for bioimaging (I. H. El-Sayed et al., Nano Letters 5(5) (2005): 829-834; K. C. Black et al., Mol. Imaging 7(1) (2008): 50-57). When gold NPs absorb light energy, they also release heat, potentially making them useful in photothermal therapy applications targeting cancer (T. B. Huff et al, Nanomedicine 2(1) (2007): 125-132) and bacterial cells (S. E. Norman et al., Nano letters 8(1) (2008): 302-306.
However, the use of metal NPs for medical diagnosis and treatment is limited, because NPs cannot be fully integrated into the biological realm without tailored control over their surface chemistry. Biomolecules and cells interact through a multitude of chemical interactions and physical forces which have not evolved in the presence of noble metals, and therefore interactions between biological systems and metal NPs are non-specific. In order to realize the full biomedical potential of gold nanoparticles, the nanoparticles must interact specifically with biological matter, including cell surface components. Furthermore, nanoparticle aggregation and nonspecific interactions with molecular and cellular constituents of the biological system must be minimized. Thus, there is a need in the art for metal nanoparticles that can be readily modified to precisely control their electromagnetic and biofunctional properties.